The zonula occludens (pl., zonulae occludentes) represents the most apical component in the junctional complex between epithelial cells.
The zonula occludens is created by localized sealing of adjacent plasma membranes
Examination of the zonula occludens or tight junction with the transmission electron microscope (TEM) reveals a narrow region in which the plasma membranes of adjoining cells come in close contact to seal off the intercellular space
(Fig. 4.9a). The high-resolution TEM similarly reveals that the zonula occludens is not a continuous seal but rather a series of focal fusions between the cells. These focal fusions are created by specific transmembrane proteins of adjoining cells that traverse the cell membrane and join in the intercellular space. The transmembrane protein occludin has been identified as the sealing protein. The cytoplasmic portion of occludin is associated with the zonula occludens proteins ZO-1, ZO-2, and ZO-3 (Fig. 4.9b,c). Occludin interacts with the actin cytoskeleton through ZO-1. Regulatory functions during the formation of the zonula occludens have been suggested for all ZO proteins. In addition, ZO-1 is a tumor suppressor, and ZO-2 is required in the epidermal growth factor-receptor signaling mechanism. The ZO-3 protein interacts with ZO-1 and the cytoplasmic domain of occludin. Many pathogenic agents, such as cytomegalovirus (CMV) and cholera toxins, act on ZO-1 and ZO-2, causing the junction to become permeable.
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